Hexokinase-2 (HK2) (HK2)

Hexokinase-2 (HK2) is a pivotal enzyme in cellular metabolism, catalyzing the first step of glycolysis by phosphorylating glucose to glucose-6-phosphate. In many cancer cells, HK2 is highly overexpressed and physically associates with the Voltage-Dependent Anion Channel (VDAC) on the outer mitochondrial membrane, forming the hexokinase-2–associated mitochondrial complex [1][2]. This association facilitates the Warburg effect by providing HK2 with direct access to mitochondrially derived ATP and simultaneously suppresses apoptosis by preventing the release of pro-apoptotic factors like cytochrome c [3]. Because of its dual role in promoting metabolic flux and cell survival, the HK2-mitochondrial complex is a significant therapeutic target in oncology [4]. Pharmacological strategies include small molecule inhibitors of its catalytic activity or agents that displace HK2 from the mitochondria, thereby sensitizing cancer cells to chemotherapy and inducing cell death [5].

Other names

HKIIHexokinase type IIMuscle hexokinaseHK2-VDAC complex

Inhibition of the catalytic activity of hexokinase-2 and the disruption of its physical association with the voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane, which triggers mitochondrial-mediated apoptosis and reduces glycolytic flux.